Advanced non-small cell lung cancer (NSCLC) is the most common cause of cancer death for both men and women in the United States. In 2005 it is estimated that there will be over 170,000 new cases of NSCLC. Most patients are diagnosed with advanced disease and the median survival for these patients ranges from 8 to 10 months. Combination chemotherapy is the standard of care for patients with advanced NSCLC, but little progress towards improving the efficacy of chemotherapy has been made in the last 20 years.
Inhibitors of the epidermal growth factor receptor (EGFR) have emerged as therapies for some patients with NSCLC. Ubiquitin Specific Protease 8 (USP8), also known as ubiquitin specific peptidase 8 and as ubiquitin carboxyl terminal hydrolase 8, is implicated in the regulation of EGFR (Berlin et al. J Biol Chem. 2010 Nov. 5;285(45):34909-21). Byun et al. have shown that inhibition of USP8 activity or reduction in USP8 expression can selectively kill NSCLC cells (Clin Cancer Res. 2013 Jul. 15;19(14):3894-904). Thus, there is a need for effective USP8 inhibitors for the treatment of non-small cell lung cancer.
Approximately 2.5 million men in the United States are living with prostate cancer. Although survival has increased significantly in the past decade, more than 28,000 men die of metastatic castration-resistant prostate cancer (mCRPC) each year. Androgen deprivation in the form of castration, either medical or surgical, remains the backbone of prostate cancer treatment. Nevertheless, most prostate cancers eventually become resistant to traditional medical or surgical castration and require additional therapeutic interventions. Thus, there is a need for effective therapies for the treatment of prostate cancer.